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M Osborn

Publications and source records attributed to M Osborn.

At least 109 records · Page 6Linked to original sources
PubMed1988

Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type.

A combined hepatocellular-cholangiocarcinoma (CHC) of transitional subtype and the surrounding cirrhotic liver tissue were investigated immunocytochemically by monoclonal antibodies specific for each of the keratin polypeptides 7, 8, 18 and 19. Different keratin subsets were found in different parts of the tumour. The hepatocellular component reveals keratins 8 and 18, with the bordering cells of trabecular formations additionally expressing keratins 7 and 19. The same keratins i.e. 7, 8, 18, 19 were found in normal bile duct epithelium as well as in cholangiocarcinomatous and transitional areas of hepatocellular and cholangiocellular differentiation. Normal hepatocytes express only keratin 8 and 18. In cirrhotic liver some modified hepatocytes additionally express keratin 7. When ductal transformation is observed in the marginal parts of portal tracts and fibrous septa the keratin polypeptide pattern mimics that of bile duct epithelium. The cholangiocellular metaplasia of hepatocytes observed here correlates well with findings in hepato-organogenesis and hepatocarcinogenesis and suggests that the transitional subtype of combined hepatocellular-cholangiocarcinoma is a variant of hepatocellular carcinoma.

Adenoma, Bile Duct↗
PubMed1988

The submembranous location of p11 and its interaction with the p36 substrate of pp60 src kinase in situ.

p36, a major cytoplasmic substrate of pp60 src kinase, is present beneath the plasma membrane. It can be isolated either as a monomer or as a heterotetramer (protein I) containing two copies each of p36 and a unique p11 polypeptide. To compare the expression rules of p36 and p11 as well as their cellular distributions, monoclonal antibodies to the two porcine proteins were isolated. In tissue culture cells p11-specific antibodies decorated the same submembranous compartment previously seen with antibodies to p36 and fodrin or spectrin and followed the p36 images under all fixation/extraction conditions tested. Immunofluorescence microscopy on tissue sections showed coincident expression patterns of both proteins confirming and extending previous results with p36 antibodies. Antibodies with limited cross-species reaction have been used to trace the fate of porcine p11 and p36 injected into cultured cells. Both proteins are incorporated in the submembranous compartment, where they remain in Triton cytoskeletons prepared in the presence but not in the absence of Ca2+. The incorporation of p36 in vivo conforms with its Ca2+-dependent binding to actin, fodrin, and certain phospholipids in vitro. In contrast, the incorporation of p11 seems to depend on an in situ interaction with p36 or an exchange with endogenous p11 present on p36. The combined results indicate a strong coupling of p11 and p36 in cellular compartmentalization and tissue differentiation.

Animals↗
PubMed1988

The organization of titin filaments in the half-sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten nonrepetitive epitopes starting at the Z line extends close to the M line.

mAbs specific for titin or nebulin were characterized by immunoblotting and fluorescence microscopy. Immunoelectron microscopy on relaxed chicken breast muscle revealed unique transverse striping patterns. Each of the 10 distinct titin antibodies provided a pair of delicate decoration lines per sarcomere. The position of these pairs was centrally symmetric to the M line and was antibody dependent. The results provided a linear epitope map, which starts at the Z line (antibody T20), covers five distinct positions along the I band (T21, T12, T4, T1, T11), the A-I junction (T3), and three distinct positions within the A band (T10, T22, T23). The epitope of T23 locates 0.2 micron before the M line. In immunoblots, the two antibodies decorating at or just before the Z line (T20, T21) specifically recognized the insoluble titin TI component but did not recognize TII, a proteolytic derivative. All other titin antibodies recognized TI and TII. Thus titin molecules appear as polar structures lacking over large regions repetitive epitopes. One physical end seems related to Z line anchorage, while the other may bind close to the M line. Titin epitopes influenced by the contractional state of the sarcomere locate between the N1 line and the A-I junction (T4, T1, T11). We discuss the results in relation to titin molecules having half-sarcomere lengths. The three nebulin antibodies so far characterized again give rise to distinct pairs of stripes. These locate close to the N2 line.

Animals↗
PubMed1987

Nebulin and titin expression in Duchenne muscular dystrophy appears normal.

Monoclonal antibodies which recognize different epitopes on either titin or nebulin show normal staining patterns on frozen sections of three muscle biopsies of Duchenne muscular dystrophy (DMD). Gel electrophoresis and immunoblotting performed on two of these muscle biopsies show the normal pattern of titin and nebulin polypeptides. Since the donor of one of these biopsies has a large deletion of the 5'-region of the DMD gene, our results argue against the recent proposal that nebulin is the gene mutated in DMD.

Antibodies, Monoclonal↗
PubMed1987

Psychiatric disorder and gynaecological symptoms in middle aged women: a community survey.

In a community survey 521 women aged 35-59 were selected at random from all patients registered in two groups practices. They were interviewed at home and assessed by means of standardised psychiatric measures and detailed gynaecological inquiry. Levels of psychiatric morbidity were found to be within the expected range for such a sample. Both psychiatric morbidity and the personality dimension of neuroticism were significantly associated with gynaecological symptoms, including dysmenorrhoea and premenstrual tension, some symptoms of excessive menstruation, and flushes and sweats but not disappearance of menstruation for over six months. Current psychiatric state was significantly associated with recent adverse life events and with indices of psychiatric vulnerability (neuroticism and previous psychiatric history), suggesting possible aetiological links with gynaecological symptoms. The findings of this study have implications for the management of gynaecological complaints in general practice.

Adult↗
PubMed1987

Chlamydia trachomatis and reactive arthritis: the missing link.

Reactive inflammatory arthritis is a common sequel to sexually acquired non-gonococcal genital-tract infection. Approximately 50% of cases are associated with Chlamydia trachomatis infection in the genital tract, although conventional cultures of joint material are sterile. Synovium, synovial-fluid cells, or both, from eight patients with sexually acquired reactive arthritis (SARA) and eight with knee effusions associated with other rheumatic diseases were examined by means of a fluorescein-labelled monoclonal antibody to C trachomatis ('Micro Trak'; Syva). Typical chlamydial elementary bodies were seen in joint material from five patients with SARA but in none of the controls. An inclusion-like cluster of elementary bodies was seen in one synovial biopsy sample. All five patients had high titres of serum chlamydial antibody. It is likely that the synovitis of SARA results directly from the presence of chlamydial elementary bodies in the joint.

Adult↗
PubMed1987

Intermediate filaments in cytological specimens of thyroid tumors.

Cytological specimens of thyroid carcinomas and follicular adenomas obtained by fine-needle aspiration biopsies or touch imprints were investigated with antibodies to keratin, vimentin, and neurofilaments. All tumors were keratin positive. In follicular adenomas as well as in papillary thyroid carcinomas, a coexpression of keratin and vimentin was detected; in follicular carcinomas, only some tumors showed coexpression of keratin and vimentin; and in medullary thyroid carcinomas, positive staining of all six tumors studied was seen with the keratin and neurofilament antibodies, with some tumors also showing coexpression of vimentin. The mechanisms of such coexpression is unclear.

Adenocarcinoma↗
PubMed1987

Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques.

Different regions of human aorta and of other human arteries obtained at autopsy were analyzed with regard to their topography and to the different stages of arteriosclerosis. Material was studied by immunocytochemical techniques with antibodies specific for either desmin (D) or for vimentin (V), the two types of intermediate filament proteins present in vascular smooth muscle cells. In normal arteries endothelial cells as well as the adjacent intimal cells were D-V+. In the media D+V+ as well as D-V+ cells were present, with the relative numbers of each cell type dependent on the particular blood vessel. When cells in arteriosclerotic plaques at different stages of development were examined an occasional plaque showed cells of the D+V+ type. In the majority of plaques however the cells were V-D+. In plaques where severe ulceration and necrotic material was present D-V+ cells were found at the border of the lesion: foam cells when they could be identified appeared to be D-V+.

Adult↗
PubMed1987

Cytoplasmic intermediate filament proteins and the nuclear lamins A, B and C share the IFA epitope.

The murine monoclonal antibody IFA isolated by Pruss et al. (Cell 27 (1981) 419) reacts with all major proteins of the cytoplasmic intermediate filament family (IF) albeit with different affinities but leaves the nucleus undecorated in standard immunofluorescence microscopy. Here we show that IFA reacts with all three nuclear lamins from rat and man in immunoblotting. This is most easily demonstrated in a cell line in which most cells lack cytoplasmic IFs. Thus the rather minor but ubiquitous 66 kD polypeptides identified by Pruss et al. as IF-associated proteins reflect the lamin triplet. While surprising at first, these results are in agreement with the approximate location of the IFA epitope on IF molecules and the recently discovered sequence homology along the rod domain between lamins A and C and IF proteins. Our results extend this relation to lamin B in spite of its unique behaviour during mitosis.

Animals↗
PubMed1987

Actin typing of rhabdomyosarcomas shows the presence of the fetal and adult forms of sarcomeric muscle actin.

We analyzed actin expression in two human rhabdomyosarcomas as well as in three rhabdomyosarcomas induced in rats by the injection of nickel sulfide. All five tumors exhibited appreciable amounts of the sarcomeric alpha-actin types, in line with their myogenic differentiation. The level of these actins was particularly high in the rat tumors, which according to morphological criteria, all showed a higher degree of differentiation than the human tumors. Interestingly, in both human tumors and in two of the three rat tumors, the level of the cardiac alpha-actin type was significantly higher than that of adult skeletal muscle alpha-actin. Taken together with the results of recent reports indicating that the cardiac alpha-actin type is a marker of embryonic and fetal skeletal muscle, our findings indicate that rhabdomyosarcomas express the embryonic sarcomeric actin isoform.

Actins↗
PubMed1987

Keratin filament disruption in interphase and mitotic cells--how is it induced?

We have studied the lability of keratin intermediate filaments in epithelial cell lines to try to understand the molecular mechanism that cause the ultrastructural transition from 10 nm filaments to the ball-like aggregates containing 2 to 3 nm filaments. Our results suggest that different growth conditions used in different laboratories may explain some but not all of the discrepancies in the literature on mitotic keratin filament disruption. Such disruption is not only cell type, but also subclone dependent and can be manipulated in one instance by altering the NaHCO3 concentration of the growth medium. An apparently similar filament to aggregate transition can be induced in interphase cells of some epithelial cell lines by incubation in a cold hypotonic buffer, or when cells are pretreated with phorbol ester and then incubated in cold physiological saline. A putative dialyzable and heat-stable factor present in medium conditioned by the growth of particular epithelial cell types may be required for disruption. Keratin polypeptide phosphorylation may play a role in filament labilization.

Animals↗
PubMed1987

Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects.

Five monoclonal antibodies recognizing different keratin polypeptides in immunoblotting or different epithelial cell types in complex tissues were studied for their suitability as reagents for the differential diagnosis of primary and secondary malignant epithelial liver tumors. The broad specificity keratin antibodies lu-5 and KL-1 stained all epithelial liver neoplasms. In contrast the antibodies CK-7 (Ker-7-specific), CK-2 (Ker-18-specific) and KA-4 (Ker-19-specific in liver) allow these neoplasms to be divided into three groups: Hepatocellular carcinomas were CK-2-positive and CK-7-negative. Cholangiocellular carcinomas, liver metastases of extrahepatic bile duct carcinomas, liver metastases of a ductal carcinoma of breast, and a follicular thyroid carcinoma were stained positively by CK-2, CK-7, and KA-4. In 1 of 6 hepatocellular carcinomas neoplastic hepatocytes were focally labeled by KA-4. In a focal nodular hyperplasia of the liver modified hepatocytes were decorated not only by CK-2 but also by CK-7 and KA-4. Liver metastases of colorectal adenocarcinomas and of a carcinoid tumor were stained positively by CK-2 and KA-4 but not by CK-7.

Adenoma, Bile Duct↗
PubMed1987

Coexpression of keratin and vimentin in damaged and regenerating tubular epithelia of the kidney.

Most renal cell carcinomas coexpress vimentin and keratin, while renal tubular epithelia express only keratin. Investigation of the intermediate filament composition of tubular epithelia in diseased rat and human kidneys now shows that altered tubular epithelia unequivocally coexpress keratin and vimentin. In rats, pronounced coexpression of vimentin and keratin was observed in chronic nephrosis induced by daunomycin, and the extent of coexpression seemed to increase with the incidence of altered collapsed and cystically dilated tubules and with the degree of tubular epithelial proliferation. It was also seen during tubular regeneration after acute tubulotoxic injury induced by mercury chloride poisoning, with vimentin expression being lost in fully regenerated tubular epithelium. In man, expression was seen in chronically and irreversibly damaged kidneys. Thus, vimentin can be expressed temporarily in acutely and reversibly damaged kidneys and chronically in irreversibly damaged kidneys. Vimentin could perhaps be regarded as an indicator of the regenerating and proliferating activity of tubular lesions.

Animals↗